tbuckley/cabot-search huggingface dataset:
Out-of-pocket costs burden for cancer treatment toxicities and symptoms management in Italy: A prospective, multicenter pilot study.
Authors: Giusti Raffaele, Marco Filetti, Pasquale Lombardi, Gabriella Gentile, Paolo Toccaceli, Guglielmo Fumi, Denise Vacca, Emilia Colpani, Giulio Ravoni, Gennaro Daniele, Giampiero Porzio
Journal: Journal of Clinical Oncology (2023)

12105 Background: Financial Toxicity (FT) refers to the financial burden and stress experienced by cancer patients as a result of the high costs associated with their treatment and care. This burden can significantly impact patients and families, affecting not only their financial well-being but also their physical and mental health. With the increasing cost of cancer care, FT has become a primary concern for those affected by the disease. Although there have been plenty of studies on the cost of cancer drugs and policy issues relating to curbing these increasing costs, studies on addressing FT in individual patients for drug-related toxicity and symptom management are still lacking. Methods: From January to October 2022, we conducted a cross-sectional, descriptive study to identify patient-administered drugs used to manage cancer treatment toxicities or cancer-associated symptoms. We recognize six common symptoms (anorexia/cachexia, fatigue, nausea and vomiting, pain, constipation, and diarrhea). All social and demographic data, including information on gender, age, performance status, education, and income, have been gathered and recorded. We collected information about the type of cancer disease and active treatment (on/off). Symptom assessment and financial distress were analyzed by administering the PERSONS and COST questionnaires, respectively, at the time of enrollment. Results: A total of 211 patients were enrolled and completed the questionnaires. 28/211 patients (13%) do not take any medications to control symptoms. Of the remaining 183 taking at least one prescription for managing these symptoms, 90% (165) pay for at least part of these drugs. Most frequently, patients assumed medicines for controlling pain (45%) and constipation (28%). Unlike all the other drug categories, these medicines correlate with financial distress (p &gt; 0.0001 and p &gt; 0.001). None of the following variables (age, type of tumor, and work situation) significantly interacted with COST and PERSONS at the univariate analyses. In contrast, a lower level of education significantly associates with the worst COST and PERSONS scores (p &gt; 0.0001). As expected, patients in palliative home care have a higher mean score for symptom burden than those without home care and, surprisingly, a higher financial distress score. Conclusions: Our results identify cancer pain and constipation as the most incident and challenging problems associated with cancer diagnosis and treatment. Moreover, they ultimately lead to a higher financial hardship due to patient self-prescribing and out-of-pocket purchases of over-the-counter drugs to control them. In our population, a lower education level is an independent risk factor for developing financial distress.
Outcomes of patients with advanced NF1-mutant melanoma treated with MEK inhibitors.
Authors: Lin Wang, Kevin B. Kim, Mohammed Kashani-Sabet, Prasad R. Dighe, Ali Aboosaiedi
Journal: Journal of Clinical Oncology (2023)

e21513 Background: Mutations in neurofibromin 1 ( NF1) constitute the third most frequent driver mutation in melanoma, occurring in approximately 15% of patients. NF1 is a tumor suppressor gene that negatively regulates the MAPK pathway by inactivating RAS through the hydrolysis of RAS-GTP to the inactive form, RAS-GDP. Preclinical studies have demonstrated that NF1 mutations induce the activation of the MAPK pathway through constitutively maintaining the active form of RAS protein, and that MEK inhibitors cause growth arrest of NF1-mutant melanoma in vitro and tumor regressions in vivo. Methods: We conducted a retrospective analysis to evaluate the outcomes of patients with NF1-mutant melanoma who were treated with MEK inhibitors using our institutional melanoma database. We searched for all melanoma patients whose melanoma was analyzed with next generation sequencing (NGS), and their clinical, pathological and molecular characteristics were examined along with the details of MEK inhibitor treatment and clinical outcomes. Results: Among 229 patients whose melanoma was analyzed with the NGS, we identified 32 patients whose melanoma harbored a pathogenic or likely pathogenic NF1 mutation, of which four were treated with trametinib. The clinical, molecular characteristics and the outcomes of the 4 patients are summarized in the table. All had previously experienced disease progression following anti-PD1 antibody therapy. One patient with metastatic mucosal melanoma had a confirmed partial response to trametinib treatment with time to progression of 18 months. Two patients had regression of the metastatic lesions at the initial tumor response evaluation, but due to significant toxicity, treatment was discontinued. Their disease progressed within 3 months after treatment discontinuation. Two patients with initial tumor regression had a mucosal primary melanoma. Interestingly, the patient with a prolonged response had the highest variant allele frequency (VAF) of NF1 whereas the early progressor had the lowest VAF (Table). All responders (including the unconfirmed responders) had a VAF of &gt;35%. Conclusions: Despite the small sample size, our findings suggest a potential promising efficacy of trametinib in the setting of NF1-mutant melanoma, particularly those with high allelic frequency, thereby providing a strong rationale for a prospective study to evaluate the clinical efficacy of MEK inhibitors in this molecular subtype of melanoma. [Table: see text]
One-year reductions in cisplatin-related chronic kidney disease (CKD) in patients with head and neck (HNC) cancer treated with avasopasem manganese: A prespecified analysis from the phase 3 ROMAN trial.
Authors: Bryan G. Allen, Douglas R. Spitz, Kranti A. Mapuskar, Diana Zepeda-Orozco, Robert Alan Beardsley, Eugene Paul Kennedy, Carryn M. Anderson
Journal: Journal of Clinical Oncology (2023)

6066 Background: Cisplatin-induced acute kidney injury (AKI), acute kidney disease (AKD), and chronic kidney disease (CKD) are associated with increased production of reactive oxygen species, notably superoxide, in conjunction with alterations in mitochondrial electron transport chain complex activities in tubular epithelial cells (Mapuskar et al. Antioxidants 2021;10:1329). These pathologies can be targeted and thereby inhibited by increasing superoxide dismutase activity, which converts superoxide to hydrogen peroxide. The investigational new drug avasopasem manganese (AVA), a selective dismutase mimetic, ameliorated cisplatin-induced kidney injury in mice (Mapuskar et al. Redox Biol 2019;20:98). Preclinical results also demonstrate that AVA does not interfere with cisplatin anticancer activity (Mohanty et al. Cancer Res 2018;78[13_suppl]:Abstract 2929). Consistent with this, a retrospective analysis of 1- and 2-year kidney function of a limited subset of patients treated in a randomized, placebo (PBO)-controlled phase 2b trial of AVA to reduce severe oral mucositis (SOM) from radiotherapy and cisplatin (CRT) suggested that AVA prevented or reduced cisplatin-related CKD compared to PBO (Steinbach et al. J Clin Oncol 2020;38[15_suppl]:Abstract 12071). Methods: The ROMAN phase 3 trial (NCT03689712; ITT n = 407) of CRT in combination with AVA or PBO demonstrated improved incidence, duration, and onset of SOM by AVA (n = 241) vs PBO (n = 166) (Anderson et al. J Clin Oncol 2022;40[16_suppl]:Abstract 6005). In ROMAN, prospectively defined follow-up of serum creatinine (sCr) and estimated glomerular filtration rates (eGFR) were assessed every 3 months for 1 year following 7 weeks of CRT. Results: At 1-year follow-up, AVA was associated with significant improvements in preservation of eGFR ( P= 0.0008) and sCr ( P= 0.006) levels vs PBO. Grade 3+ CKD (eGFR &lt; 60 mL/min) results through 12 months show 10% AVA vs 20% PBO (relative risk 0.55, P= 0.0043). Regarding cisplatin schedule, patients receiving Q3W therapy show grade 3+ CKD of 12% AVA vs 22% PBO; patients receiving QW therapy show AVA 9% vs PBO 19%. During treatment, nominal reduction of the incidence of AKI adverse events (0.8% AVA vs 3.6% PBO) was also observed. Conclusions: At 1-year follow-up, AVA appears to reduce cisplatin-related CKD in the study population and may also reduce cisplatin-related AKI during treatment. These results carry significance beyond CRT for HNC, potentially impacting platinum-containing regimens in other cancers. Clinical trial information: NCT03689712 .
Disparities in uptake of novel therapies for acute myeloid leukemia.
Authors: Andrew Hantel, Colin Cernik, Hajime Uno, Thomas Walsh, Kasisomayajula Viswanath, Christopher S. Lathan, Daniel J. DeAngelo, Gregory A. Abel
Journal: Journal of Clinical Oncology (2023)

6540 Background: Multiple novel therapies have recently been approved to treat acute myeloid leukemia (AML). Inequities in the uptake of novel treatments have been seen in other cancers but are not known for this population. Methods: We performed a retrospective analysis of the nationwide Flatiron Health electronic health record (EHR)-derived deidentified database. We assessed sociodemographic associations with novel AML therapies use within two-years of Food and Drug Administration (FDA) approval from 1/2014-8/2022. Therapies were: glasdegib, venetoclax, ivosidenib, midostaurin, CPX-351, gilteritinib, enasidenib, and gemtuzumab ozogamicin (GO). Univariable associations were assessed using X 2 testing. Logistic regression modeling of community practices assessed associations between novel therapy receipt and sociodemographics adjusted by treatment year. Variable categories are shown. Results: Of 8081 patients in 280 clinics, 3102 (38%) received at least one novel therapy. The cohort was predominately older (69; interquartile range [57, 77]), male (56%), non-Hispanic (NH)-White (88%), and treated at a community practice (75%). There were 4808 patients treated within 24-months of a novel therapy approval, of which 1937 (40%) received a novel therapy. Venetoclax represented 59% of novel treatments prescribed. Bivariate associations were seen between novel therapy receipt within 24-months of approval and high SES and non-Hispanic (NH)-White race-ethnicity; similar associations were seen when assessed at the treatment regimen level. In a logistic regression model of community practices (N=2,459), older patients (OR 1.01; 95%CI 1.00, 1.02), females (OR 1.2; 95% CI 1.0,1.4), and those from high (vs low) SES (OR 1.4; 95%CI 1.1, 1.6) were more likely to receive novel therapy; there were no associations with sex or race-ethnicity. Conclusions: In this large national database of adults with AML, almost half received novel therapy within 24-months of FDA approval. Though there was no dichotomous difference in uptake by race-ethnicity in community practices, younger and more affluent patients were more likely to receive novel therapy, concerning for disparities in uptake. [Table: see text]
Predictive factors of early death in older women with gynecological cancer: A prospective cohort study.
Authors: Jurema Telles O. Lima, Letícia telles Sales, Emanuel P. B. Lima, MAria Eduarda M. Gonçalves, Jose Iran Costa, Lucas P. Gonsioroski, Mirella Rebello, Zilda Cavalcanti, Maria Julia Gonçalves Mello
Journal: Journal of Clinical Oncology (2023)

e24034 Background: Comprehensive geriatric assessment (CGA) correlate with risk of early mortality in older adult patients. Methods: a prospective cohort study. older woman with a recent diagnosis of gynecological cancer were from eight community hospitals and cancer center in Northeast Brazil and were recruited during their first medical appointment at the outpatient oncologic clinic. A basal CGA was done before the treatment decision (ADL, Charlson Comorbidity Index- CCI, Karnofsky Performance status – KPS, GDS15, IPAQ, MMSE, MNA, MNA-SF, PS, PPS, Polipharmacy, QLQc30, TUG). During the follow up of six months, information about the treatments performed, the targeted interventions and early death was collected. Overall survival was estimated using the Kaplan–Meier method, and survival curves were compared using the Log rank test for categorical variables. A multivariate Cox proportional hazards model was used to select early death risk factors. Results: 274 patients with a median age of 72 years, 13.5% died within 180 days. 29,7% cervical cancer, 122 (44,5%),endometrial cancer, 53(19,3%) ovary cancer and 17( 6,2%) vulvar cancer. The mean global QL was higher among survivors and the probability of survival was higher in patients who had better QL (p &lt; 0.001). After adjustments for risk factors (cervical cancer topography, metastatic disease and Karnofsky ≤ 50), Global QoL was a protective factor (HR = 0.99; 95%CI 0.98-1.00; p = 0.031). Cervical cancer topography 95%CI HR = 2.28 1.18-4.40 p = 0.014). MNA &lt; 17 95 %CIHR = 9.72 (3.85-24.50 , p &lt; 0.001) TUG ( HR = 3,87 ; 95 % CI 1,93 - 7,74 p = 0.004). Conclusions: A better score in the Global QoL assessment , a good nutritional status by MNA and low risk of falls by TUG were protective factor for early death in older women with gynecological cancer.Cervical cancer is the highest risk of early death topography. Risk factors for early death can be identified in the admission of older women with gynecological cancer, allowing better care planning.
Risk stratification tools to help decide on adjuvant chemotherapy usage in resected soft tissue sarcomas: A 10 year review of an Irish sarcoma centre experience.
Authors: Catherine Weadick, Rachel J Keogh, Caitriona Goggin, Jake Murphy, Linda Feeley, Michael William Bennett, Seamus O'Reilly, Henry Paul Redmond, Jason Kelly, Deirdre O'Mahony, Sinead Noonan, Jim Clover, Richard Martin Bambury
Journal: Journal of Clinical Oncology (2023)

11575 Background: Soft tissue sarcoma (STS) is comprised of 80 pathologic subtypes based on a combination of distinctive morphological, immunohistochemical and molecular features. Adult-type soft tissue and visceral sarcomas are rare, with an estimated incidence of 4-5/100,000/year in Europe. The National Comprehensive Cancer Network (NCCN) guidelines recommend consideration of neo-adjuvant or adjuvant systemic treatment in resectable stage III (high grade tumours which are &gt;5cm) and also in those who need to undergo an amputation or radical resection with adverse functional outcomes. The Sarculator risk prediction tool has identified a threshold of risk above which the administration of chemotherapy may provide an overall survival benefit. This can be applied to the most common histologic subtypes. Patients affected by these subtypes and with a 10-year predicted OS likelihood &lt;60% are considered as high risk and therefore, should be considered for adjuvant chemotherapy. Alternatively, tumours considered at high risk of recurrence based on size &gt;5cm and high grade histology, may benefit from adjuvant chemotherapy. Therefore, the aim of this project is to review the outcomes of resected extremity/trunk soft tissue sarcoma and assess the prognostic accuracy of these risk prediction methods. Methods: All new patients with resected STS discussed in the STS MDT in Cork University Hospital between Jan 2012 – Dec 2021 were identified. The histology and imaging of the identified patients were reviewed. Data regarding demographics, histology, treatment and outcomes was collected. Risk assessment using AJCC and Sarculator score was done on all patients with an extremity or trunk sarcoma. Overall survival was recorded and assessed including Kaplan Meier method for time to event analysis. Results: 200 patients were identified as having an STS resected - 134 of these were located on the trunk or extremities representing 24 different histological subtypes. Sarculator score was calculated for 60 of these (well differentiated liposarcomas, desmoid tumours, and dermatofibrosarcoma protuberans were excluded). 3 patients received adjuvant chemotherapy and 4 patient neoadjuvant chemotherapy. Overall survival data is presented below. Conclusions: Our cohort is representative of the broad histological subtypes expected in sarcoma. Sarculator score results correlate with international outcomes, with higher scores associated with increased mortality. In our cohort, sarculator score was more predictive of outcome than tumour grade/size alone. [Table: see text]
Osimertinib then chemotherapy in EGFR-mutated lung cancer with osimertinib third-line rechallenge (OCELOT).
Authors: Daniel Adam Breadner, Mark David Vincent, Geoffrey Liu, Jeffrey Rothenstein, Ines B. Menjak, Parneet Kaur Cheema, Rosalyn A. Juergens, Hamid Mithoowani, Puneet Bains, Ying Wang, Paul Wheatley-Price
Journal: Journal of Clinical Oncology (2023)

TPS9160 Background: The results of the FLAURA study established osimertinib as the new first-line standard of care for patients with the two ‘common’ types of epidermal growth factor receptor mutation-positive (EGFR+) advanced non-small-cell lung cancer (aNSCLC). Second-line (2L) treatment is typically platinum pemetrexed chemotherapy and the standard third-line (3L) treatment is docetaxel throughout much of the globe, which has a modest response rate of 7 – 15%. Previously, when first generation (1G) EGFR tyrosine kinase inhibitor (TKIs) were standard of care in the first-line setting, a number of prospective and retrospective studies examined 3L rechallenge with the same 1G EGFR TKI following 2L chemotherapy, with varying levels of success. Osimertinib is a well-tolerated EGFR TKI which is active against the T790M resistance mutation, which would have limited the efficacy of rechallenge with 1G EGFR TKIs. Methods: This is a multicentered international phase II investigator-initiated study of osimertinib in the 3L rechallenge of patients with EGFR+ aNSCLC, following 1L treatment with osimertinib and 2L therapy with platinum pemetrexed chemotherapy. A maximum of 255 patients will be enrolled. Patients with ‘common’ EGFR exon 19 deletions or L858R mutations will enroll at the start of 2L chemotherapy or 3L osimertinib rechallenge. The primary objective is 3L objective response rate (ORR) in the first 100 evaluable patients, according to RECIST 1.1. Secondary objectives include disease control rate (DCR), progression free survival (PFS), time to treatment failure, overall survival and toxicity for 3L osimertinib rechallenge. Exploratory objectives include assessment of osimertinib resistance based on serial ctDNA samples collected from all participants. The OCELOT study, NCT04335292, is actively enrolling participants. Clinical trial information: NCT04335292 .
Statin use for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in breast cancer (BC) patients (pts).
Authors: John W. Melson, Benjamin Koethe, Sharanya Mohanty, Seda Babroudi, Chen Bao, Amar Chunduru, Henry Dwaah, Matthew Finn, Annika Jain, Mumtu Lalla, Paras Patnaik, Rachael Studley, Rachel J. Buchsbaum, Kathryn Huber, Susan K. Parsons, Jenica N Upshaw
Journal: Journal of Clinical Oncology (2023)

e24051 Background: CVD is the leading cause of non-cancer mortality for BC survivors. Clinical practice guidelines support the assessment and management of ASCVD risk factors among BC pts, including lipid-lowering therapy when indicated. We performed a single-institution, retrospective, longitudinal study of ASCVD risk factors and statin use for primary and secondary ASCVD prevention among BC pts. Methods: Pts diagnosed with BC from 2009-2015 were identified from the institutional cancer registry. Pts with non-metastatic BC or ductal carcinoma in situ and at least 2 years of follow up were included. Records were reviewed at 12-month intervals from BC diagnosis until last follow up or the study end date of 12/31/19. BC characteristics and treatment, prevalent and incident CV risk factors, CV diagnoses, CV medications, and CV events were manually abstracted and confirmed by a second reviewer. 10-year estimated ASCVD risk, based on non-laboratory predictors, was calculated for each pt. Chi-square tests were performed to assess the relationship between race/ethnicity, age category, and statin exposure. Results: 326 pts were included (median age at diagnosis 60.7 yrs; 67% White, 16% Asian (Chinese), 10% Black; 54% with stage I disease). At baseline, 53% had hypertension, 40% had hyperlipidemia, 37% were former or current smokers, 32% had a BMI ≥30, 7% had a history of ASCVD, and 5% had a family history of premature coronary artery disease. 52% received radiation therapy. 114 pts had radiation dosimetry available; 59 (18%) received a mean heart dose ≥1 Gy. Median follow up was 6.5 yrs. At the time of BC diagnosis, 64% of pts had an established indication for lipid-lowering therapy: history of ASCVD, diabetes, or estimated 10-year ASCVD risk ≥7.5% (Table). Of these pts with an indication for statin, 35% were prescribed a statin at baseline and 57% were prescribed a statin at any time during the study period. No association between baseline statin exposure and pt age category (X 2 = 3.75, p = 0.290) or race/ethnicity (X 2 = 2.64, p = 0.562) was observed. Among 11% of pts with ASCVD at any time, 83% were prescribed a statin but only 40% received a guideline-recommended high-intensity statin. Conclusions: A majority of pts in our study were candidates for statin therapy for primary or secondary ASCVD prevention at the time of BC diagnosis. 43% were never prescribed a statin, predominantly pts whose indication was primary prevention. There is opportunity for improvement in ASCVD prevention during BC treatment and follow up. [Table: see text]